PMID- 24968020 OWN - NLM STAT- MEDLINE DCOM- 20150221 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 6 DP - 2014 TI - Injury-associated PACAP expression in rat sensory and motor neurons is induced by endogenous BDNF. PG - e100730 LID - 10.1371/journal.pone.0100730 [doi] LID - e100730 AB - Peripheral nerve injury results in dramatic upregulation in pituitary adenylate cyclase activating polypeptide (PACAP) expression in adult rat dorsal root ganglia and spinal motor neurons mirroring that described for the neurotrophin brain derived neurotrophic factor (BDNF). Thus, we posited that injury-associated alterations in BDNF expression regulate the changes in PACAP expression observed in the injured neurons. The role of endogenous BDNF in induction and/or maintenance of PACAP mRNA expression in injured adult rat motor and sensory neurons was examined by intrathecally infusing or intraperitoneally injecting BDNF-specific antibodies or control IgGs immediately at the time of L4-L6 spinal nerve injury, or in a delayed fashion one week later for 3 days followed by analysis of impact on PACAP expression. PACAP mRNA in injured lumbar sensory and motor neurons was detected using in situ hybridization, allowing quantification of relative changes between experimental groups, with ATF-3 immunofluorescence serving to identify the injured subpopulation of motor neurons. Both the incidence and level of PACAP mRNA expression were dramatically reduced in injured sensory and motor neurons in response to immediate intrathecal anti-BDNF treatment. In contrast, neither intraperitoneal injections nor delayed intrathecal infusions of anti-BDNF had any discernible impact on PACAP expression. This impact on PACAP expression in response to BDNF immunoneutralization in DRG was confirmed using qRT-PCR or by using BDNF selective siRNAs to reduce neuronal BDNF expression. Collectively, our findings support that endogenous injury-associated BDNF expression is critically involved in induction, but not maintenance, of injury-associated PACAP expression in sensory and motor neurons. FAU - Pettersson, Lina M E AU - Pettersson LM AD - CMSNRC & Department of Anatomy & Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada. FAU - Geremia, Nicole M AU - Geremia NM AD - CMSNRC & Department of Anatomy & Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada. FAU - Ying, Zhengxin AU - Ying Z AD - CMSNRC & Department of Anatomy & Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada. FAU - Verge, Valerie M K AU - Verge VM AD - CMSNRC & Department of Anatomy & Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada. LA - eng GR - MOP74747/Canadian Institutes of Health Research/Canada GR - ROP102801/Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140626 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Antibody Specificity MH - Brain-Derived Neurotrophic Factor/immunology/*metabolism MH - *Gene Expression Regulation MH - Male MH - Motor Neurons/*metabolism MH - Peripheral Nerve Injuries/*genetics/metabolism/*pathology MH - Pituitary Adenylate Cyclase-Activating Polypeptide/*genetics MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Sciatic Nerve/injuries MH - Sensory Receptor Cells/*metabolism PMC - PMC4072603 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/06/27 06:00 MHDA- 2015/02/24 06:00 PMCR- 2014/06/26 CRDT- 2014/06/27 06:00 PHST- 2014/05/15 00:00 [received] PHST- 2014/05/28 00:00 [accepted] PHST- 2014/06/27 06:00 [entrez] PHST- 2014/06/27 06:00 [pubmed] PHST- 2015/02/24 06:00 [medline] PHST- 2014/06/26 00:00 [pmc-release] AID - PONE-D-14-09000 [pii] AID - 10.1371/journal.pone.0100730 [doi] PST - epublish SO - PLoS One. 2014 Jun 26;9(6):e100730. doi: 10.1371/journal.pone.0100730. eCollection 2014.